A new animal model of systemic sclerosis

一种新的系统性硬化症动物模型

• 批准号: 24659522
• 负责人: SATO Shinichi
• 金额: $ 2.41万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Challenging Exploratory Research
• 财政年份: 2012
• 资助国家: 日本
• 起止时间: 2012-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-24659522/
• 关键词: 全身性強皮症; トポイソメラーゼI; 完全フロイドアジュバンド; IL-6; 皮膚硬化; 肺線維化; 自己免疫; 免疫学

To assess the contribution of anti-DNA topoisomerase I(anti-topo I)antibody, tissue fibrosis and cytokine production were examined in mice treated with topo I and either Freund's complete adjuvant (CFA) or Freund's incomplete adjuvant(IFA).Treatment with topo I and CFA,in contrast to treatment with topo I and IFA,induced skin and lung fibrosis with increased interleukin (IL)-6 and IL-17 production. Anti-topo I antibody levels were greater in mice treated with topo I and CFA than with topo I and IFA.Furthermore,treatment with topo I and CFA increased Th2 and Th17 cell frequencies in bronchoalveolar lavage fluid,whereas treatment with topo I and IFA increased Th1 and Treg cell frequencies.Moreover,loss of IL-6 expression ameliorated skin and lung fibrosis and decreased Th2 and Th17 cell frequencies. This study shows that treatment with topo I and CFA induces SSc-like tissue fibrosis and autoimmunity.

为了评估抗DNA拓扑异构酶I（anti-topo I）抗体的贡献，在用topo I和弗氏完全佐剂（CFA）或弗氏不完全佐剂（IFA）处理的小鼠中检查组织纤维化和细胞因子产生。与用topo I和IFA处理相比，用topo I和CFA处理诱导皮肤和肺纤维化，同时增加白细胞介素（IL）-6和IL-17产生。Topo I和CFA处理组小鼠的抗Topo I抗体水平高于Topo I和IFA处理组; Topo I和CFA处理组小鼠支气管肺泡灌洗液中Th 2和Th 17细胞频率增加，而Topo I和IFA处理组小鼠支气管肺泡灌洗液中Th 1和Treg细胞频率增加; IL-6表达缺失可改善皮肤和肺纤维化，并降低Th 2和Th 17细胞频率。这项研究表明，用topo I和CFA治疗诱导Ssc样组织纤维化和自身免疫。

项目成果

Increased production of soluble inducible costimulator in patients with diffuse cutaneous systemic sclerosis

• DOI: 10.1007/s00403-012-1292-7
• 发表时间: 2013-01-01
• 期刊: ARCHIVES OF DERMATOLOGICAL RESEARCH
• 影响因子: 3
• 作者: Yanaba, Koichi;Asano, Yoshihide;Sato, Shinichi
• 通讯作者: Sato, Shinichi

Serum adiponectin levels inversely correlate with the activity of progressive skin sclerosis in patients with diffuse cutaneous systemic sclerosis

• DOI: 10.1111/j.1468-3083.2011.04077.x
• 发表时间: 2012-03-01
• 期刊: JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY AND VENEREOLOGY
• 影响因子: 9.2
• 作者: Masui, Y.;Asano, Y.;Kadono, T.
• 通讯作者: Kadono, T.

Investigation of prognostic factors for skin sclerosis and lungfunction in Japanese patients with early systemic prospect observational study.sclerosis : a multicentre

通过早期系统性前景观察性研究研究日本患者皮肤硬化和肺功能的预后因素。硬化：多中心

• 发表时间: 2012
• 期刊: Rheumatology (Oxford)
• 作者: Hasegawa M;Asano Y;Endo H;Fujimoto M;Goto D;Ihn H;Inoue K;Ishikawa O;Kawaguchi Y;Kuwana M;Muro Y;Ogawa F;Sasaki T;Takahashi H;Tanaka S;Takehara K;Sato S.
• 通讯作者: Sato S.

Clinical significance of monitoring serum adiponectin levels during intravenous pulse cyclophosphamide therapy in interstitial lung disease associated with systemic sclerosis

• DOI: 10.1007/s10165-012-0660-7
• 发表时间: 2013-03-01
• 期刊: MODERN RHEUMATOLOGY
• 影响因子: 2.2
• 作者: Masui, Yuri;Asano, Yoshihide;Kadono, Takafumi
• 通讯作者: Kadono, Takafumi

Serum levels of ADAM12‐S: possible association with the initiation and progression of dermal fibrosis and interstitial lung disease in patients with systemic sclerosis

• DOI: 10.1111/j.1468-3083.2012.04558.x
• 发表时间: 2013-06
• 期刊: Journal of the European Academy of Dermatology and Venereology
• 影响因子: 9.2
• 作者: T. Taniguchi;Y. Asano;K. Akamata;N. Aozasa;S. Noda;T. Takahashi;Y. Ichimura;T. Toyama;H. Sumida;Y. Kuwano;K. Yanaba;Y. Tada;M. Sugaya;T. Kadono;S. Sato